Hepatocellular carcinoma in the elderly: Meta-analysis and systematic literature review

Table 1 Prevalence of viral hepatitis among included studies

Study	Treatment	HBsAg positive (P = 0.023)		HCV Ab positive (P = 0.1681)
		Young	Elderly	Young	Elderly
Yau et al[27]	SR/RFA/TACE	86.00%	52.00%	NA	NA
Chen et al[7]	SR	58.50%	28.60%	NA	NA
Hanazaki et al[8]	SR	23.70%	18.40%	40.70%	55.40%
Yeh et al[9]	SR	74.00%	25.80%	31.80%	63.20%
Ferrero et al[10]	SR	21.40%	10.90%	38.90%	60.90%
Kaibori et al[11]	SR	20.10%	9.70%	69.40%	71.60%
Oishi et al[4]	SR	23.70%	1.56%	66.00%	70.00%
Huang et al[12]	SR	88.80%	65.70%	1.10%	7.50%
Mirici-Cappa et al[13]	SR	15.00%	7.10%	47.10%	57.10%
Tsujita et al[14]	SR	23.00%	8.70%	70.60%	87.00%
Yamada et al[15]	SR	27.30%	36.30%	57.70%	54.50%
Nishikawa et al[16]	SR	17.50%	4.35%	56.30%	66.30%
Hirokawa et al[17]	SR	NA	NA	68.00%	50.00%
Ide et al[18]	SR	21.90%	12.50%	65.10%	68.80%
Liu et al[20]	SR	68.00%	33.00%	23.00%	36.00%
Kishida et al[21]	SR	31.00%	5.00%	43.00%	55.00%
Kim et al[22]	SR	64.50%	28.80%	7.80%	18.60%
Takahashi et al[24]	RFA	1.00%	6.80%	82.70%	93.40%
Mirici-Cappa et al[13]	RFA	13.00%	5.60%	52.20%	74.40%
Nishikawa et al[25]	RFA	11.30%	1.54%	73.90%	86.90%
Liu et al[20]	RFA	48.00%	43.00%	43.00%	39.00%
Fujiwara et al[26]	RFA	13.50%	3.70%	70.40%	79.60%
Yau et al[27]	TACE	87.00%	63.00%	10.00%	18.00%
Mirici-Cappa et al[13]	TACE	11.30%	12.10%	51.70%	59.90%
Liu et al[20]	TACE	52.00%	37.00%	35.00%	35.00%
Nishikawa et al[28]	TACE	15.50%	0.00%	58.30%	71.20%

TACE: Transarterial chemoembolization; RFA: Radiofrequency ablation; NA: Not available; HBsAg: Hepatitis B surface antigen; HCV: Hepatitis C virus.

Table 2 Preoperative data of patients with hepatocellular carcinoma who underwent surgical resection

Author	Year	Country	Design	Age cut off	Young, n	Elderly, n	Sex: male/female (P = 0.6947)		Child Pugh A/B		Tumor size (cm)(P = 0.984)
							Y	E	Y	E	Y	E
Yau et al[27]	1999	China	Prospective	70	299	31	255/44	21/10	285/14	30/1	7.9	8.0
Wu et al[8]	1999	Taiwan	Retrospective	80	239	21	190/49	19/2	194/34	16/4	6.5	7.0
Hanazaki et al[8]	2001	Japan	Retrospective	70	283	103	222/61	71/32	226/56	76/27	NA	NA
Yeh et al[9]	2004	Taiwan	Prospective	70	398	34	310/88	27/7	152/199	12/18	6.7	5.5
Ferrero et al[10]	2005	Italy	Prospective	70	177	64	145/32	47/17	138/37	54/8	NA	NA
Kaibori et al[11]	2009	Japan	Retrospective	70	333	155	269/64	119/36	302/31	139/16	4.32	3.76
Oishi et al[4]	2009	Japan	Prospective	75	502	64	381/121	48/16	427/NA	59/NA	3.3	3.9
Huang et al[12]	2009	China	Retrospective	70	268	67	222/46	58/9	257/11	63/4	7.4	7.3
Mirici-Cappa et al[13]	2009	Italy	Retrospective	70	43	142	116/26	32/11	123/18	40/3	4.09	3.42
Tsujita et al[14]	2012	Japan	Prospective	80	385	23	253/132	15/8	264/121	18/5	3.2	3.5
Yamada et al[15]	2012	Japan	Prospective	80	267	11	205/62	6/5	245/22	9/2	4.8	5.2
Nishikawa et al[16]	2013	Japan	Prospective	75	206	92	161/45	61/31	198/8	90/2	4.8	4.6
Hirokawa et al[17]	2013	Japan	Retrospective	70	120	100	99/21	69/31	98/22	88/12	3.0	3.5
Ide et al[18]	2013	Japan	Retrospective	75	192	64	157/35	43/21	168/24	57/7	4.9	4.9
Taniai et al[19]	2013	Japan	Retrospective	75	353	63	271/82	39/24	265/84	56/7	NA	NA
Liu et al[20]	2014	Taiwan	Prospective	75	730	129	571/159	107/22	694/36	116/13	NA	NA
Kishida et al[21]	2015	Japan	Retrospective	75	82	22	66/16	20/2	NA	NA	3.0	3.5
Kim et al[22]	2015	South Korea	Retrospective	70	219	60	168/51	46/14	NA	NA	4.9	4.9

NA: Not available; E: Elderly; Y: Young.

Table 3 Co-morbidities of patients with hepatocellular carcinoma who underwent surgical resection

Author	Year	Country	CV co-morbidities (P = 0.341)		Resp co-morbidities (P = 0.031)		Diabetes (P = 0.086)		Alcohol (P = 0.737)
			Young	Elderly	Young	Elderly	Young	Elderly	Young	Elderly
Yau et al[27]	1999	China	NA	NA	NA	NA	NA	NA	NA	NA
Chen et al[7]	1999	Taiwan	47.60%	12.60%	8.40%	14.30%	5.40%	14.30%	NA	NA
Hanazaki et al[8]	2001	Japan	11.00%	24.30%	7.40%	19.40%	8.50%	31.10%	NA	NA
Yeh et al[9]	2004	Taiwan	NA	NA	NA	NA	15.30%	38.20%	NA	NA
Ferrero et al[10]	2005	Italy	NA	NA	NA	NA	NA	NA	31.10%	20.30%
Kaibori et al[11]	2009	Japan	16%	39%	4%	16%	7%	23.00%	48.30%	35.40%
Oishi et al[4]	2009	Japan	NA	NA	NA	NA	NA	NA	NA	NA
Huang et al[12]	2009	China	NA	NA	NA	NA	NA	NA	NA	NA
Mirici-Cappa et al[13]	2009	Italy	NA	NA	NA	NA	NA	NA	12.90%	21.40%
Tsujita et al[14]	2012	Japan	11.90%	22.00%	13.00%	8.70%	29.40%	21.70%	NA	NA
Yamada et al[15]	2012	Japan	NA	NA	NA	NA	NA	NA	NA	NA
Nishikawa et al[16]	2013	Japan	13.10%	50.80%	10.70%	15.20%	33.50%	26.00%	NA	NA
Hirokawa et al[17]	2013	Japan	NA	NA	NA	NA	NA	NA	NA	NA
Ide et al[18]	2013	Japan	NA	NA	NA	NA	NA	NA	NA	NA
Taniai et al[19]	2013	Japan	NA	NA	NA	NA	NA	NA	NA	NA
Liu et al[20]	2014	Taiwan	NA	NA	NA	NA	NA	NA	15.00%	10.00%
Kishida et al[21]	2015	Japan	NA	NA	NA	NA	NA	NA	16.00%	18.00%
Kim et al[22]	2015	South Korea	NA	NA	NA	NA	13.70%	25.00%	3.20%	5.10%

NA: Not available.

Table 4 Preoperative data of patients with hepatocellular carcinoma who underwent radiofrequency ablation

Author	Year	Country	Design	Treatment	Age cut off	Young, n	Elderly, n	Sex: male/female (P = 0.031)		Child Pugh A/B/C		Tumor size (cm) (P = 0.662)
								Young	Elderly	Young	Elderly	Young	Elderly
Takahashi et al[24]	2010	Japan	Prospective	RFA	75	354	107	218/136	46/61	278/76	77/30	NA	NA
Mirici-Cappa et al[13]	2010	Italy	Retrospective	RFA or PEI	70	230	195	165/65	118/77	147/70/10	157/33/2	3.04	3.13
Nishikawa et al[25]	2012	Japan	Prospective	RFA	75	238	130	150/88	67/63	145/36/4	87/16	1.92	2.31
Liu et al[20]	2014	Taiwan	Prospective	RFA	75	336	147	221/115	96/51	80/17/3	89/11	NA	NA
Fujiwara et al[26]	2014	Japan	Retrospective	RFA	75	1048	353	705/343	191/162	782/255/11	287/63/3	2.40	2.50

RFA: Radiofrequency ablation; NA: Not available.

Table 5 Co-morbidities of patients with hepatocellular carcinoma who underwent radiofrequency ablation

Author	Year	Country	Design	Age cut off	Young, n	Elderly, n	Alcohol (P = 0.031)		CV comorbidities (P = 0.446)		Resp comorbidities (P = 0.474)		DM (P = 0.602)
							Young	Elderly	Young	Elderly	Young	Elderly	Young	Elderly
Takahashi et al[24]	2010	Japan	Prospective	75	354	107	24.9%	8.4%	7.9%	13.1%	3.4%	9.3%	21.4%	16.8%
Mirici-Cappa et al[13]	2010	Italy	Retrospective	70	230	195	12.6%	5.6%	NA	NA	NA	NA	NA	NA
Nishikawa et al[25]	2012	Japan	Prospective	75	238	130	NA	NA	15.1%	34.6%	13.9%	25.4%	34.9%	28.5%
Liu et al[20]	2014	Taiwan	Prospective	75	336	147	19.0%	10.0%	NA	NA	NA	NA	NA	NA
Fujiwara et al[26]	2014	Japan	Retrospective	75	1048	353	15.9%	11.9%	NA	NA	NA	NA	NA	NA

NA: Not available.

Table 6 Survival data comparing elderly and younger patients undergoing radiofrequency ablation

Author	Year	Young, n	Elderly, n	1-yr overall survival		3-yr overall survival		5-yr overall survival		P value
				Young	Elderly	Young	Elderly	Young	Elderly
Takahashi et al[24]	2010	354	107	NA	NA	80.0%	82.0%	63.0%	61.0%	0.824
Mirici-Cappa et al[13]	2010	230	195	89.9%	90.1%	52.9%	53.4%	35.1%	29.0%	0.797
Nishikawa et al[25]	2012	238	130	97.6%	90.0%	83.7%	64.1%	64.0%	44.8%	0.001
Liu et al[21]	2014	336	147	95.0%	96.0%	81.0%	78.0%	65.0%	65.0%	0.690
Fujiwara et al[26]	2014	1048	353	97.3%	95.5%	82.3%	75.6%	62.9%	52.7%	< 0.001

NA: Not available.

Table 7 Preoperative data of patients undergoing transarterial chemoembolization

Author	Year	Country	Design	Tx	Age cut off	Young, n	Elderly, n	Sex: male/female (P = 0.272)		Child Pugh A/B/C		Tumor size (cm) (P = 0.953)
								Young	Elderly	Young	Elderly	Young	Elderly
Yau et al[27]	2009	China	Prospective	TACE	70	317	67	272/45	54/13	262/55	52/15	8.70	8.50
Yau et al[27]	2009	China	Prospective	TACE	70	843	197	715/128	143/54	674/159/10	165/32	NA	NA
Mirici-Cappa et al[13]	2010	Italy	Retrospective	TACE	70	396	158	301/95	117/41	234/135/21	113/40/3	3.89	3.86
Liu et al[20]	2014	Taiwan	Prospective	TACE	75	604	271	446/158	222/49	72/22/3	86/14	NA	NA
Nishikawa et al[28]	2014	Japan	Prospective	TACE	75	84	66	63/21	34/32	52/32	53/13	5.10	5.70

TACE: Transarterial chemoembolization; NA: Not available.

Table 8 Survival data comparing elderly and younger patients undergoing transarterial chemoembolization

Author	Age cut off	Young, n	Elderly, n	Median survival (mo) (P = 0.683)		Post Op complication (P = 0.854)		30-d mortality (P = 0.698)		1-yr overall survival		3-yr overall survival		5-yr overall survival		P value
				Y	E	Y	E	Y	E	Y	E	Y	E	Y	E
Yau et al[27]	70	317	67	9	12	26.0%	24.0%	5.0%	7.0%	41.0%	53.0%	18.0%	25.0%	13.0%	17.0%	0.277
Yau et al[27]	70	843	197	8.1	14	26.9%	24.4%	3.5%	4.7%	39.2%	54.4%	14.9%	23.2%	8.4%	10.6%	< 0.003
Mirici-Cappa et al[13]	70	396	158	27	26	NA	NA	NA	NA	78.9%	79.4%	32.0%	36.4%	13.3%	6.4%	0.730
Liu et al[20]	75	604	271	NA	NA	NA	NA	NA	NA	79.0%	84.0%	57.0%	57.0%	42.0%	39.0%	0.953
Nishikawa et al[28]	75	84	66	29.3	34.8	6.0%	5.0%	0.0%	0.0%	78.2%	84.1%	39.3%	48.0%	33.8%	15.0%	0.887

Y: Young; E: Elderly; NA: Not available.